Microneedle Delivery of Heterologous Microparticulate COVID-19 Vaccine Induces Cross Strain Specific Antibody Levels in Mice

Background: In recent years, the COVID-19 pandemic has significantly impacted global health, largely driven by the emergence of various genetic mutations within the SARS-CoV-2 virus. Although the pandemic phase has passed, the full extent of the virus’s evolutionary trajectory remains uncertain, hig...

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Main Authors: Tanisha Manoj Arte, Smital Rajan Patil, Emmanuel Adediran, Revanth Singh, Priyal Bagwe, Mahek Anil Gulani, Dedeepya Pasupuleti, Amarae Ferguson, Susu M. Zughaier, Martin J. D’Souza
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Language:English
Published: MDPI AG 2025-04-01
Series:Vaccines
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Online Access:https://www.mdpi.com/2076-393X/13/4/380
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author Tanisha Manoj Arte
Smital Rajan Patil
Emmanuel Adediran
Revanth Singh
Priyal Bagwe
Mahek Anil Gulani
Dedeepya Pasupuleti
Amarae Ferguson
Susu M. Zughaier
Martin J. D’Souza
author_facet Tanisha Manoj Arte
Smital Rajan Patil
Emmanuel Adediran
Revanth Singh
Priyal Bagwe
Mahek Anil Gulani
Dedeepya Pasupuleti
Amarae Ferguson
Susu M. Zughaier
Martin J. D’Souza
author_sort Tanisha Manoj Arte
collection DOAJ
description Background: In recent years, the COVID-19 pandemic has significantly impacted global health, largely driven by the emergence of various genetic mutations within the SARS-CoV-2 virus. Although the pandemic phase has passed, the full extent of the virus’s evolutionary trajectory remains uncertain, highlighting the need for continued research in vaccine development to establish a cross-reactive approach that can effectively address different variants. This proof-of-concept study aimed to assess the effectiveness of microparticulate vaccine delivery through the minimally invasive microneedle route of administration, using a heterologous prime–booster strategy against the SARS-CoV-2 virus. Method: This strategy uses the whole inactivated virus of the Delta variant for the prime dose and the whole inactivated virus of the Omicron variant for the booster dose, with alum as an adjuvant. The formulation of microparticles involves encapsulating the antigens in poly lactic-co-glycolic acid (PLGA) polymer, which provides sustained release and enhances immunogenicity while protecting the antigen. Microparticles were tested for in vitro assays, and characterization included particle size, zeta potential, and encapsulation efficacy. Furthermore, serum was collected post-administration of the vaccine in mice and was tested for antibody levels. Result: In vitro assays confirmed the non-cytotoxicity and the ability of microparticles to activate the immune response of the vaccine particles. Administering this microparticulate vaccine via microneedles has proven effective for delivering vaccines through the skin. We also observed significantly higher antigen-specific antibody levels and cross-reactivity in the strains. Conclusions: Our adjuvanted microparticulate-based heterologous prime–booster vaccine strategy showed cross-reactivity among the strains and was successfully delivered using microneedles.
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spelling doaj-art-adefa51d2c5b4f34a1c632b306abb0ca2025-08-20T02:18:21ZengMDPI AGVaccines2076-393X2025-04-0113438010.3390/vaccines13040380Microneedle Delivery of Heterologous Microparticulate COVID-19 Vaccine Induces Cross Strain Specific Antibody Levels in MiceTanisha Manoj Arte0Smital Rajan Patil1Emmanuel Adediran2Revanth Singh3Priyal Bagwe4Mahek Anil Gulani5Dedeepya Pasupuleti6Amarae Ferguson7Susu M. Zughaier8Martin J. D’Souza9Vaccine Nanotechnology Laboratory, Center for Drug Delivery Research, College of Pharmacy, Mercer University, Atlanta, GA 30341, USAVaccine Nanotechnology Laboratory, Center for Drug Delivery Research, College of Pharmacy, Mercer University, Atlanta, GA 30341, USAVaccine Nanotechnology Laboratory, Center for Drug Delivery Research, College of Pharmacy, Mercer University, Atlanta, GA 30341, USAVaccine Nanotechnology Laboratory, Center for Drug Delivery Research, College of Pharmacy, Mercer University, Atlanta, GA 30341, USAVaccine Nanotechnology Laboratory, Center for Drug Delivery Research, College of Pharmacy, Mercer University, Atlanta, GA 30341, USAVaccine Nanotechnology Laboratory, Center for Drug Delivery Research, College of Pharmacy, Mercer University, Atlanta, GA 30341, USAVaccine Nanotechnology Laboratory, Center for Drug Delivery Research, College of Pharmacy, Mercer University, Atlanta, GA 30341, USAVaccine Nanotechnology Laboratory, Center for Drug Delivery Research, College of Pharmacy, Mercer University, Atlanta, GA 30341, USACollege of Medicine, Qatar University, Doha P. O. Box 2713, QatarVaccine Nanotechnology Laboratory, Center for Drug Delivery Research, College of Pharmacy, Mercer University, Atlanta, GA 30341, USABackground: In recent years, the COVID-19 pandemic has significantly impacted global health, largely driven by the emergence of various genetic mutations within the SARS-CoV-2 virus. Although the pandemic phase has passed, the full extent of the virus’s evolutionary trajectory remains uncertain, highlighting the need for continued research in vaccine development to establish a cross-reactive approach that can effectively address different variants. This proof-of-concept study aimed to assess the effectiveness of microparticulate vaccine delivery through the minimally invasive microneedle route of administration, using a heterologous prime–booster strategy against the SARS-CoV-2 virus. Method: This strategy uses the whole inactivated virus of the Delta variant for the prime dose and the whole inactivated virus of the Omicron variant for the booster dose, with alum as an adjuvant. The formulation of microparticles involves encapsulating the antigens in poly lactic-co-glycolic acid (PLGA) polymer, which provides sustained release and enhances immunogenicity while protecting the antigen. Microparticles were tested for in vitro assays, and characterization included particle size, zeta potential, and encapsulation efficacy. Furthermore, serum was collected post-administration of the vaccine in mice and was tested for antibody levels. Result: In vitro assays confirmed the non-cytotoxicity and the ability of microparticles to activate the immune response of the vaccine particles. Administering this microparticulate vaccine via microneedles has proven effective for delivering vaccines through the skin. We also observed significantly higher antigen-specific antibody levels and cross-reactivity in the strains. Conclusions: Our adjuvanted microparticulate-based heterologous prime–booster vaccine strategy showed cross-reactivity among the strains and was successfully delivered using microneedles.https://www.mdpi.com/2076-393X/13/4/380SARS-COV-2heterologous vaccinemicroparticlesmicroneedleshumoral antibody responseOmicron
spellingShingle Tanisha Manoj Arte
Smital Rajan Patil
Emmanuel Adediran
Revanth Singh
Priyal Bagwe
Mahek Anil Gulani
Dedeepya Pasupuleti
Amarae Ferguson
Susu M. Zughaier
Martin J. D’Souza
Microneedle Delivery of Heterologous Microparticulate COVID-19 Vaccine Induces Cross Strain Specific Antibody Levels in Mice
Vaccines
SARS-COV-2
heterologous vaccine
microparticles
microneedles
humoral antibody response
Omicron
title Microneedle Delivery of Heterologous Microparticulate COVID-19 Vaccine Induces Cross Strain Specific Antibody Levels in Mice
title_full Microneedle Delivery of Heterologous Microparticulate COVID-19 Vaccine Induces Cross Strain Specific Antibody Levels in Mice
title_fullStr Microneedle Delivery of Heterologous Microparticulate COVID-19 Vaccine Induces Cross Strain Specific Antibody Levels in Mice
title_full_unstemmed Microneedle Delivery of Heterologous Microparticulate COVID-19 Vaccine Induces Cross Strain Specific Antibody Levels in Mice
title_short Microneedle Delivery of Heterologous Microparticulate COVID-19 Vaccine Induces Cross Strain Specific Antibody Levels in Mice
title_sort microneedle delivery of heterologous microparticulate covid 19 vaccine induces cross strain specific antibody levels in mice
topic SARS-COV-2
heterologous vaccine
microparticles
microneedles
humoral antibody response
Omicron
url https://www.mdpi.com/2076-393X/13/4/380
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